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The following Key Messages comprise the salient findings of this study:1. Ambient energy (from sun, air, ground, and sky) can heat and cool buildings; provide hot water, ventilation, and daylighting; dry clothes; and cook food. These services account for about three-quarters of building energy consumption and a third of total US demand. Biophilic design (direct and indirect connections with nature) is an intrinsic adjunct to ambient energy systems, and improves wellness and human performance.2. The current strategy of electrification and energy efficiency for buildings will not meet our climate goals, because the transition to an all-renewable electric grid is too slow. Widespread adoption of ambient energy is needed. Solar-heated buildings also flatten the seasonal demand for electricity compared to all-electric buildings, reducing required production capacity and long-term energy storage. In addition, ambient-conditioned buildings improve resilience by remaining livable during power outages.3. National policies, incentives, and marketing should be enacted to promote ambient energy use. Federal administrative priorities should reflect the importance of ambient energy for buildings. Use of ambient energy should be encouraged through existing and new building codes and standards.4. Ambient energy system design tools are needed for architects, engineers, builders, building scientists, realtors, appraisers, and consumers. PVWatts is used over 100 million times per year for photovoltaic system design. A similar, simple, and accessible tool for ambient design is crucial.5. Training on ambient energy is needed throughout secondary, post-secondary, and continuing education for workforce development. Currently, only about 10% of colleges teach courses on passive heating and cooling systems.6. Ambient-conditioned buildings should be demonstrated in all US climate zones. Performance should be monitored and reported, with quantitative case studies made widely available.7. While current technology is sufficient to build high-performance ambient buildings now, research is needed to develop new technologies to harness ambient energy more effectively and more economically. Such advancements will facilitate adoption of ambient energy technologies in a wider range of buildings, including retrofits. Examples include windows with much lower thermal losses, use of the building shell for thermal storage, alternative light-weight thermal storage systems, sky-radiation cooling systems, automated controls for solar gains and passive cooling, and ground coupling.

The summer drought in the United Kingdom (UK) in 2022 produced significant speculation concerning how its termination may impact and interact with the soil resource. Whilst knowledge regarding soils and droughts exists in the scientific literature, a coherent understanding of the wider range of impacts on soil properties and functions has not been compiled for temperate soils. Here, we draw together knowledge from studies in the UK and other temperate countries to understand how soils respond to drought, and importantly what and where our knowledge gaps are. First, we define the different types of droughts and their frequency in the UK and provide a brief overview on the likely societal impacts that droughts place on the soil and related ecosystems. Our focus is on ‘agricultural and ecosystem drought’, as this is when soils experience dry periods affecting crops and ecosystem function, followed by rewetting. The behaviour of moisture in soils and the key processes that contribute to its storage and transport are examined. The principal changes in the physical, chemical, and biological properties of soils resulting from drought, and rewetting (i.e., drought termination) are discussed and their extensive interactions are demonstrated. Processes that are involved in the rewetting of soils are explored for soil and catchment-scale soil responses. Lastly, soils’ recovery after drought is considered, knowledge gaps are identified, and areas to improve understanding are highlighted.

This case report investigates the potential use of metabolism as a sensitive biomarker in monitoring the effectiveness of anti-amyloid therapy in a patient with mild cognitive impairment due to early Alzheimer's disease. The study centers around a 74-year-old male patient treated with aducanumab, a monoclonal antibody developed for anti-amyloid therapy. Alongside an expected decline in cerebral amyloid monitored using PET amyloid tracers, we observed significant improvements in the patient's brain metabolic activity, measured via 18-fluorodeoxyglucose positron emission tomography (FDG PET). Despite limitations posed by the single-patient case study, the findings invite further research and consider the utilization of FDG PET as a surrogate for clinically meaningful changes in the treatment of early Alzheimer's disease. These findings suggest the potential for more personalized and effective therapeutic interventions.

Abstract Numerous spatiotemporal species distribution modeling frameworks are now available to the ecological practitioner. This study compared three such frameworks accessible in the R programming language: generalized additive models with spatiotemporal smooths as implemented by mgcv, spatiotemporal generalized linear mixed models based on nearest neighbor Gaussian processes as implemented by starve, and spatiotemporal generalized linear mixed models based on the stochastic partial differential equations approach as implemented by sdmTMB. The primary focus was to compare the inferences obtained from applying these frameworks to the case study of the orange‐footed sea cucumber, Cucumaria frondosa, on the Scotian Shelf off Nova Scotia, Canada. Each model was fit to catch data (2000–2019) from Fisheries and Oceans Canada's annual Research Vessel and Snow Crab surveys. Environmental covariates were sourced from high‐resolution data layers, including physical oceanographic, bathymetric, and seafloor morphometric datasets. The three models captured variability in sea cucumber distribution that would have been overlooked without a spatiotemporal approach. Although their predictions were similar, including within C. frondosa spatial reserves, the models provided different inferences regarding covariate effects. This suggests that while practitioners primarily interested in mapping species distributions need only apply the most familiar framework, those most concerned with identifying predictive environmental covariates may benefit from comparing the output from multiple approaches. Employing multiple approaches can also serve as a validation technique.

Introduction With a limited global supply of vaccines and an increasing vaccine hesitancy, improving vaccination coverage has become a priority. Current vaccination regimes require multiple doses to be administered in a defined schedule where missed doses may lead to incomplete vaccine coverage and failure of immunization programmes. As such, there is an ever-increasing demand to convert multi-dose injectable vaccines into single-dose formats, often called single administration vaccines (SAVs). Areas covered This review summarizes recent developments in the field of SAVs, with a focus on pulsatile or controlled-release formulations. It will identify the technical challenges, translational as well as commercial barriers to SAVs development. Furthermore, the progress of SAV formulations for hepatitis B and polio vaccines will be reviewed thoroughly as case studies, with a focus on the development challenges and the preclinical immunogenicity/reactogenicity data. Expert opinion Despite the efforts to develop SAVs, few attempts have advanced to Phase-I trials. Considering the SAV development journey and bottlenecks, including commercial barriers from the early stages, may overcome some of the hurdles around the technology. The renewed global focus on vaccines since the COVID-19 pandemic could facilitate development of a new generation of technologies for pandemic preparedness including strategies for SAVs.

Background: Efficacy of nonoperative treatment for rotator cuff tears has been debated, especially for full-thickness tears. The purpose of this study was to a) define the minimal clinically important difference (MCID) of nonoperative treatment with regard to Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference (PI) and upper extremity (UE), and b) determine the proportion of patients with both partial and full-thickness tears (PTRCT, FTRCT) who achieve this improvement following initial nonoperative treatment. We hypothesized that >75% of PTRCT and FTRTC patients would achieve MCID for PROMIS PI and UE. Methods: We performed a retrospective cohort study evaluating nonoperatively managed patients with image-confirmed PTRCT and FTRCT. Treatment modalities and follow-up PROMIS scores at least 6 months after their initial visit were recorded. Using a distribution technique, MCID was calculated. Results: A total of 111 FTRCT and 68 PTRCT patients were included with at least 6 months of follow-up. At 6 months from initial presentation, the MCID for PROMIS UE was 3.75 and 3.95 for FTRCT and PTRCT patients, respectively. For PROMIS PI, the MCID was 3.35 and 3.90 for FTRCT and PTRCT, respectively. In total, 41% of FTRCT and 41% of PTRCT achieved MCID for PROMIS UE. Thirty-four percent of FTRCT and 35% of PTRCT achieved MCID for PROMIS PI. Conclusion: The majority of patients undergoing nonoperative treatment for supraspinatus/infraspinatus rotator cuff tears did not achieve MCID at 6 months for PROMIS PI (34% for FTRCT and 35% for PTRCT) or UE (41% for FTRCT and 41% for PTRCT).

Macadamia nuts are, economically, the second most important crop in the state of Hawai’i. A recent decline in yield and acreage has been attributed to insect damage and diseases such as Macadamia Quick Decline (MQD) caused by Phytophthora tropicalis and P. heveae. To develop an improved methodology for the diagnosis and treatment of MQD, investigations were undertaken to better understand the pathosystem of the disease. These investigations included sampling from multiple locations from sectioned trees utilizing two methods of tissue collection and isolations using two baiting techniques. The collection of tissue from the cambium and phloem of trees after scraping away the bark and in locations of recent or current sap exudation using a narrow diameter steel awl proved to be an efficient means for the molecular detection of the MQD pathogens from infected trees exhibiting MQD symptoms. In addition, a more efficient and cost-effective baiting method using apple puree was developed.

Abstract Perennial bioenergy crops are a key tool in decarbonizing global energy systems, but to ensure the efficient use of land resources, it is essential that yields and crop longevity are maximized. Remedial shallow surface tillage is being explored in commercial Miscanthus plantations as an approach to reinvigorate older crops and to rectify poor establishment, improving yields. There are posited links, however, between tillage and losses in soil carbon (C) via increased ecosystem C fluxes to the atmosphere. As Miscanthus is utilized as an energy crop, changes in field C fluxes need to be assessed as part of the C balance of the crop. Here, for the first time, we quantify the C impacts of remedial tillage at a mature commercial Miscanthus plantation in Lincolnshire, United Kingdom. Net ecosystem C production based on eddy covariance flux observations and exported yield totalled 12.16 Mg C ha−1 over the 4.6 year period after tillage, showing the site functioned as a net sink for atmospheric carbon dioxide (CO2). There was no indication of negative tillage induced impacts on soil C stocks, with no difference 3 years post tillage in the surface (0–30 cm) or deep (0–70 cm) soil C stocks between the tilled Miscanthus field and an adjacent paired untilled Miscanthus field. Comparison to historic samples showed surface soil C stocks increased by 11.16 ± 3.91 Mg C ha−1 between pre (October 2011) and post tillage sampling (November 2016). Within the period of the study, however, the tillage did not result in the increased yields necessary to “pay back” the tillage induced yield loss. Rather the crop was effectively re‐established, with progressive yield increases over the study period, mirroring expectations of newly planted sites. The overall impacts of remedial tillage will depend therefore, on the longer‐term impacts on crop longevity and yields.

Rapid Ohia Death (ROD) is caused by two pathogens, Ceratocystis lukuohia and Ceratocystis huliohia. The established species-specific real-time PCR assays targeting the single-copy cerato-platanin gene require DNA from between 2 and 16 spores per reaction for consistent detection, which is suitable for analysis of infected plant tissue but not sensitive enough to consistently detect low spore loads in environmental samples. Here, we present two redesigned qPCR assays targeting the first internal transcribed spacer (ITS) region of the multi-copy ribosomal DNA operon from the respective species, both capable of consistent detection of the pathogen at concentrations as low as 1 fg per reaction, less than the size of the haploid genome. Due to this increased sensitivity, these ITS qPCR assays are superior for analysis of DNA extracted from material collected in airborne particle samplers and from soil. Here, we demonstrate the utility of these qPCR assays for the characterization of windblown and soilborne dispersal of the pathogens, which is critical for the development of management practices that mitigate disease spread. [Figure: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.

Abstract Background A glymphatic system has been proposed that comprises flow that enters along cerebral paraarterial channels between the artery wall and the surrounding glial layer, continues through the parenchyma, and then exits along similar paravenous channels. The mechanism driving flow through this system is unclear. The pulsatile (oscillatory plus mean) flow measured in the space surrounding the middle cerebral artery (MCA) suggests that peristalsis created by intravascular blood pressure pulses is a candidate for the paraarterial flow in the subarachnoid spaces. However, peristalsis is ineffective in driving significant mean flow when the amplitude of channel wall motion is small, as has been observed in the MCA artery wall. In this paper, peristalsis in combination with two additional mechanisms, a longitudinal pressure gradient and directional flow resistance, is evaluated to match the measured MCA paraarterial oscillatory and mean flows. Methods Two analytical models are used that simplify the paraarterial branched network to a long continuous channel with a traveling wave in order to maximize the potential effect of peristalsis on the mean flow. The two models have parallel-plate and annulus geometries, respectively, with and without an added longitudinal pressure gradient. The effect of directional flow resistors was also evaluated for the parallel-plate geometry. Results For these models, the measured amplitude of arterial wall motion is too large to cause the small measured amplitude of oscillatory velocity, indicating that the outer wall must also move. At a combined motion matching the measured oscillatory velocity, peristalsis is incapable of driving enough mean flow. Directional flow resistance elements augment the mean flow, but not enough to provide a match. With a steady longitudinal pressure gradient, both oscillatory and mean flows can be matched to the measurements. Conclusions These results suggest that peristalsis drives the oscillatory flow in the subarachnoid paraarterial space, but is incapable of driving the mean flow. The effect of directional flow resistors is insufficient to produce a match, but a small longitudinal pressure gradient is capable of creating the mean flow. Additional experiments are needed to confirm whether the outer wall also moves, as well as to validate the pressure gradient.

Nursing homes and other long-term care facilities account for a disproportionate share of COVID-19 cases and fatalities worldwide. Outbreaks in US nursing homes have persisted despite nationwide visitor restrictions beginning in mid-March. An early report issued by the Centers for Disease Control and Prevention identified staff members working in multiple nursing homes as a likely source of spread from the Life Care Center in Kirkland, WA, to other skilled nursing facilities. The full extent of staff connections between nursing homes-and the role these connections serve in spreading a highly contagious respiratory infection-is currently unknown given the lack of centralized data on cross-facility employment. We perform a large-scale analysis of nursing home connections via shared staff and contractors using device-level geolocation data from 50 million smartphones, and find that 5.1% of smartphone users who visited a nursing home for at least 1 h also visited another facility during our 11-wk study period-even after visitor restrictions were imposed. We construct network measures of connectedness and estimate that nursing homes, on average, share connections with 7.1 other facilities. Traditional federal regulatory metrics of nursing home quality are unimportant in predicting outbreaks, consistent with recent research. Controlling for demographic and other factors, a home's staff network connections and its centrality within the greater network strongly predict COVID-19 cases.

Mistrust of scientific evidence and government-issued guidelines is increasingly correlated with political affiliation. Survey evidence has documented skepticism in a diverse set of issues including climate change, vaccine hesitancy, and, most recently, COVID-19 risks. Less well understood is whether these beliefs alter high-stakes behavior. Combining GPS data for 2.7 million smartphone users in Florida and Texas with 2016 U.S. presidential election precinct-level results, we examine how conservative-media dismissals of hurricane advisories in 2017 influenced evacuation decisions. Likely Trump-voting Florida residents were 10 to 11 percentage points less likely to evacuate Hurricane Irma than Clinton voters (34% versus 45%), a gap not present in prior hurricanes. Results are robust to fine-grain geographic controls, which compare likely Clinton and Trump voters living within 150 m of each other. The rapid surge in media-led suspicion of hurricane forecasts-and the resulting divide in self-protective measures-illustrates a large behavioral consequence of science denialism.

Composite cognitive measures in large-scale studies with biomarker data for amyloid and tau have been widely used to characterize Alzheimer's disease (AD). However, little is known about how the findings from these studies translate to memory clinic populations without biomarker data, using single measures of cognition. Additionally, most studies have utilized voxel-based morphometry or limited surface-based morphometry such as cortical thickness, to measure the neurodegeneration associated with cognitive deficits. In this study, we aimed to replicate and extend the biomarker, composite study relationships using expanded surface-based morphometry and single measures of cognition in a memory clinic population. We examined 271 clinically diagnosed symptomatic individuals with mild cognitive impairment (N = 93) and Alzheimer's disease dementia (N = 178), as well as healthy controls (N = 29). Surface-based morphometry measures included cortical thickness, sulcal depth, and gyrification index within the “signature areas” of Alzheimer's disease. The cognitive variables pertained to hallmark features of Alzheimer's disease including verbal learning, verbal memory retention, and language, as well as executive function. The results demonstrated that verbal learning, language, and executive function correlated with the cortical thickness of the temporal, frontal, and parietal areas. Verbal memory retention was correlated to the thickness of temporal regions and gyrification of the inferior temporal gyrus. Language was related to the temporal regions and the supramarginal gyrus' sulcal depth and gyrification index. Executive function was correlated with the medial temporal gyrus and supramarginal gyrus sulcal depth, and the gyrification index of temporal regions and supramarginal gyrus, but not with the frontal areas. Predictions of each of these cognitive measures were dependent on a combination of structures and each of the morphometry measurements, and often included medial temporal gyrus thickness and sulcal depth. Overall, the results demonstrated that the relationships between cortical thinning and cognition are widespread and can be observed using single measures of cognition in a clinically diagnosed AD population. The utility of sulcal depth and gyrification index measures may be more focal to certain brain areas and cognitive measures. The relative importance of temporal, frontal, and parietal regions in verbal learning, language, and executive function, but not verbal memory retention, was replicated in this clinic cohort.

There is now a preponderance of evidence suggesting that the types of online course management software (OCMS) used in purely online undergraduate college courses, do not meet the needs of younger immature students. These students often lack the learning skills necessary to succeed in such courses, nor do the popular OCMS include the vigilance mechanisms to guide such students to successful course completion in the absence of face-to-face human instruction. This paper explores the literature relevant to design theory, learning theory, decision support, and vigilance, to develop a design theory as a guide to software developers and academics studying how to design future systems for the immature student in accordance with the latest research.

Pulsed power generators create high-energy-density conditions by rapidly delivering an immense pulse of electrical current to a compact imploding load. Accurately measuring the shape and amplitude of this load current pulse is essential to understanding the behavior of all pulsed power experiments. At the Z Pulsed Power Facility, the closest-in load current measurements are provided by velocimetry techniques such as VISAR (velocity interferometer system for any reflector) and PDV (photonic Doppler velocimetry). Here, fiber-coupled interferometers measure the velocity history of an exploding metallic flyer plate that is embedded in the vertical walls of the current return can. The flyer plate is driven outward by the magnetic pressure from the load current such that magnetohydrodynamic modeling can be used to determine the load current waveform from the measured velocity history. In this paper, we present the first load current velocimetry measurements to be made from the horizontal top flyer plate that carries current radially inward from the return can to the load. These spatially resolved measurements, which span R=5–9 mm, are enabled by a transformative new velocimetry diagnostic—a line-imaging velocity interferometer called Z Line VISAR (ZLV)—whose optical performance overcomes the measurement challenges presented by the steep velocity gradients encountered on the top flyer plate. To validate ZLV’s capabilities, a 14-MA, 100-ns experiment was conducted to losslessly couple current up the return can and radially inward across the top flyer plate. Comparisons between the ZLV data obtained from this experiment and two-dimensional magnetohydrodynamic simulations driven with the current measured on the return can indicate that the current delivery across the top flyer plate is indeed lossless to within the few-percent uncertainty of the ZLV data. Given that the current coupling is lossless, the experimental results are used to demonstrate that one-dimensional current unfold techniques can be applied to generate a radially resolved load current map from the ZLV velocity data. This analysis provides a template for how to use the ZLV diagnostic to determine the efficacy of current delivery in future experiments where losses may occur in close proximity to the load.

Abstract Background The fecal microbiome of healthy horses may be influenced by signalment, diet, environmental factors, and disease. Objectives To assess the effects of age, breed, sex, geographic location, season, diet, and colitis caused by antibiotic use (antimicrobial‐associated diarrhea [AAD]) and Salmonella infection on fecal microbiota. Animals Healthy horses (n = 80) were sampled from nonhospital environments across multiple geographical locations in the United States. Horses with AAD (n = 14) were defined as those that developed diarrhea secondary to antimicrobial use. Horses with Salmonella infection (n = 12) were presented with spontaneous onset of colitis and subsequently tested positive on Salmonella quantitative polymerase chain reaction. All horses were >1 year of age and stratified by a dietary scale that included forages (pasture and hay) and concentrates grouped by percentage of fiber and amount. Methods Illumina sequencing of 16S rRNA genes was performed on fecal DNA. Results Healthy horses fed higher amounts of grain clustered separately from those fed lower amounts of grain (analysis of similarities [ANOSIM], R = 0.356‐0.385, Q = 0.002). Horses with AAD and Salmonella had decreased richness and evenness compared to healthy horses (P

The Glastir Monitoring and Evaluation Programme (GMEP) ran from 2013 until 2016 and was probably the most comprehensive programme of ecological study ever undertaken at a national scale in Wales. The programme aimed to (1) set up an evaluation of the environmental effects of the Glastir agri-environment scheme and (2) quantify environmental status and trends across the wider countryside of Wales. The focus was on outcomes for climate change mitigation, biodiversity, soil and water quality, woodland expansion, and cultural landscapes. As such, GMEP included a large field-survey component, collecting data on a range of elements including vegetation, land cover and use, soils, freshwaters, birds, and insect pollinators from up to three-hundred 1 km survey squares throughout Wales. The field survey capitalised upon the UK Centre for Ecology & Hydrology (UKCEH) Countryside Survey of Great Britain, which has provided an extensive set of repeated, standardised ecological measurements since 1978. The design of both GMEP and the UKCEH Countryside Survey involved stratified-random sampling of squares from a 1 km grid, ensuring proportional representation from land classes with distinct climate, geology and physical geography. Data were collected from different land cover types and landscape features by trained professional surveyors, following standardised and published protocols. Thus, GMEP was designed so that surveys could be repeated at regular intervals to monitor the Welsh environment, including the impacts of agri-environment interventions. One such repeat survey is scheduled for 2021 under the Environment and Rural Affairs Monitoring & Modelling Programme (ERAMMP). Data from GMEP have been used to address many applied policy questions, but there is major potential for further analyses. The precise locations of data collection are not publicly available, largely for reasons of landowner confidentiality. However, the wide variety of available datasets can be (1) analysed at coarse spatial resolutions and (2) linked to each other based on square-level and plot-level identifiers, allowing exploration of relationships, trade-offs and synergies. This paper describes the key sets of raw data arising from the field survey at co-located sites (2013 to 2016). Data from each of these survey elements are available with the following digital object identifiers (DOIs): Landscape features (Maskell et al., 2020a–c), https://doi.org/10.5285/82c63533-529e-47b9-8e78-51b27028cc7f, https://doi.org/10.5285/9f8d9cc6-b552-4c8b-af09-e92743cdd3de, https://doi.org/10.5285/f481c6bf-5774-4df8-8776-c4d7bf059d40; Vegetation plots (Smart et al., 2020), https://doi.org/10.5285/71d3619c-4439-4c9e-84dc-3ca873d7f5cc; Topsoil physico-chemical properties (Robinson et al., 2019), https://doi.org/10.5285/0fa51dc6-1537-4ad6-9d06-e476c137ed09; Topsoil meso-fauna (Keith et al., 2019), https://doi.org/10.5285/1c5cf317-2f03-4fef-b060-9eccbb4d9c21; Topsoil particle size distribution (Lebron et al., 2020), https://doi.org/10.5285/d6c3cc3c-a7b7-48b2-9e61-d07454639656; Headwater stream quality metrics (Scarlett et al., 2020a), https://doi.org/10.5285/e305fa80-3d38-4576-beef-f6546fad5d45; Pond quality metrics (Scarlett et al., 2020b), https://doi.org/10.5285/687b38d3-2278-41a0-9317-2c7595d6b882; Insect pollinator and flower data (Botham et al., 2020), https://doi.org/10.5285/3c8f4e46-bf6c-4ea1-9340-571fede26ee8; and Bird counts (Siriwardena et al., 2020), https://doi.org/10.5285/31da0a94-62be-47b3-b76e-4bdef3037360.

Measurement(s) earthworm communities • Abundance • organic material • Diversity • environmental properties Technology Type(s) digital curation Factor Type(s) location Sample Characteristic - Organism Lumbricina Sample Characteristic - Environment soil Sample Characteristic - Location global Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13399118

Introduction: We investigate the association neighborhood cohesion, as source of social support, has with psychological distress among white, Black, and Latinx lesbian, gay, and bisexual (LGB) individuals, compared to heterosexual individuals in the United States. Method: We estimate zero-order multinomial logistic regression models to assess the likelihood of moderate and severe psychological distress among respondents. Result: In the models accounting for neighborhood cohesion and all other covariates, white, Black, and Latinx lesbian, gay, and bisexual individuals are more likely to meet the criteria for moderate and severe psychological distress than non-LGB people. Conclusion: Neighborhood cohesion has differing impact on psychological distress outcomes by racial/ethnic-sexual orientation groups, but in general provides a greater magnitude of protection against moderate psychological distress for non-LGB groups and a greater magnitude of protection against severe psychological distress for LGB groups.

ImportanceSeveral randomized clinical trials have demonstrated the efficacy of preexposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) acquisition. Little is known about adherence to the regimen, sexual practices, and overall effectiveness when PrEP is implemented in clinics that treat sexually transmitted infections (STIs) and community-based clinics serving men who have sex with men (MSM).ObjectiveTo assess PrEP adherence, sexual behaviors, and the incidence of STIs and HIV infection in a cohort of MSM and transgender women initiating PrEP in the United States.Design, setting, and participantsDemonstration project conducted from October 1, 2012, through February 10, 2015 (last date of follow-up), among 557 MSM and transgender women in 2 STI clinics in San Francisco, California, and Miami, Florida, and a community health center in Washington, DC. Data were analyzed from December 18, 2014, through August 8, 2015.InterventionsA combination of daily, oral tenofovir disoproxil fumarate and emtricitabine was provided free of charge for 48 weeks. All participants received HIV testing, brief client-centered counseling, and clinical monitoring.Main outcomes and measuresConcentrations of tenofovir diphosphate in dried blood spot samples, self-reported numbers of anal sex partners and episodes of condomless receptive anal sex, and incidence of STI and HIV acquisition.ResultsOverall, 557 participants initiated PrEP, and 437 of these (78.5%) were retained through 48 weeks. Based on the findings from the 294 participants who underwent measurement of tenofovir diphosphate levels, 80.0% to 85.6% had protective levels (consistent with ≥4 doses/wk) at follow-up visits. African American participants (56.8% of visits; P = .003) and those from the Miami site (65.1% of visits; P

Abstract There are posited links between the establishment of perennial bioenergy, such as short rotation coppice (SRC) willow and Miscanthus × giganteus, on low carbon soils and enhanced soil C sequestration. Sequestration provides additional climate mitigation, however, few studies have explored impacts on soil C stocks of bioenergy crop removal; thus, the permanence of any sequestered C is unclear. This uncertainty has led some authors to question the handling of soil C stocks with carbon accounting, for example, through life cycle assessments. Here, we provide additional data for this debate, reporting on the soil C impacts of the reversion (removal and return) to arable cropping of commercial SRC willow and Miscanthus across four sites in the UK, two for each bioenergy crop, with eight reversions nested within these sites. Using a paired‐site approach, soil C stocks (0–1 m) were compared between 3 and 7 years after bioenergy crop removal. Impacts on soil C stocks varied, ranging from an increase of 70.16 ± 10.81 Mg C/ha 7 years after reversion of SRC willow to a decrease of 33.38 ± 5.33 Mg C/ha 3 years after reversion of Miscanthus compared to paired arable land. The implications for carbon accounting will depend on the method used to allocate this stock change between current and past land use. However, with published life cycle assessment values for the lifetime C reduction provided by these crops ranging from 29.50 to 138.55 Mg C/ha, the magnitude of these changes in stock are significant. We discuss the potential underlying mechanisms driving variability in soil C stock change, including the age of bioenergy crop at removal, removal methods, and differences in the recalcitrant of the crop residues, and highlight the need to design management methods to limit negative outcomes.

Abstract Background Blood removal from cerebrospinal fluid (CSF) in post-subarachnoid hemorrhage patients may reduce the risk of related secondary brain injury. We formulated a computational fluid dynamics (CFD) model to investigate the impact of a dual-lumen catheter-based CSF filtration system, called Neurapheresis™ therapy, on blood removal from CSF compared to lumbar drain. Methods A subject-specific multiphase CFD model of CSF system-wide solute transport was constructed based on MRI measurements. The Neurapheresis catheter geometry was added to the model within the spinal subarachnoid space (SAS). Neurapheresis flow aspiration and return rate was 2.0 and 1.8 mL/min, versus 0.2 mL/min drainage for lumbar drain. Blood was modeled as a bulk fluid phase within CSF with a 10% initial tracer concentration and identical viscosity and density as CSF. Subject-specific oscillatory CSF flow was applied at the model inlet. The dura and spinal cord geometry were considered to be stationary. Spatial–temporal tracer concentration was quantified based on time-average steady-streaming velocities throughout the domain under Neurapheresis therapy and lumbar drain. To help verify CFD results, an optically clear in vitro CSF model was constructed with fluorescein used as a blood surrogate. Quantitative comparison of numerical and in vitro results was performed by linear regression of spatial–temporal tracer concentration over 24-h. Results After 24-h, tracer concentration was reduced to 4.9% under Neurapheresis therapy compared to 6.5% under lumbar drain. Tracer clearance was most rapid between the catheter aspiration and return ports. Neurapheresis therapy was found to have a greater impact on steady-streaming compared to lumbar drain. Steady-streaming in the cranial SAS was ~ 50× smaller than in the spinal SAS for both cases. CFD results were strongly correlated with the in vitro spatial–temporal tracer concentration under Neurapheresis therapy (R2 = 0.89 with + 2.13% and − 1.93% tracer concentration confidence interval). Conclusion A subject-specific CFD model of CSF system-wide solute transport was used to investigate the impact of Neurapheresis therapy on tracer removal from CSF compared to lumbar drain over a 24-h period. Neurapheresis therapy was found to substantially increase tracer clearance compared to lumbar drain. The multiphase CFD results were verified by in vitro fluorescein tracer experiments.

Solid dose vaccine formulation and delivery systems offer potential advantages over traditional liquid vaccine formulations. In addition to enhanced thermostability, needle-free delivery of unit solid dose injectable (USDI) vaccines offers safe, rapid, and error-free administration, with applicability to both human and animal health. Solid dose formulation technologies can be adapted for delivery of different vaccine formats including live attenuated vaccines, which remain the ‘gold standard’ for many disease targets. Porcine reproductive and respiratory syndrome viruses (PRRSV) cause one of the most economically important diseases affecting the global pig industry. Despite several shortcomings, live attenuated vaccines are widely used to control PRRSV. We optimised a freeze-dried USDI formulation of live attenuated PRRSV-1, which fully retained infectious titre, and evaluated its immunogenicity in comparison to virus delivered in liquid suspension via intramuscular and subcutaneous needle inoculation. Pigs vaccinated with the USDI formulation displayed vaccine viraemia, and PRRSV-specific antibody and T cell responses comparable to animals immunised with the liquid vaccine. The USDI vaccine formulation was stable for at least 6 months when stored refrigerated. These data demonstrate the potential for a solid dose vaccine delivery system as an alternative to conventional needle-syringe delivery of live attenuated PRRSV vaccines.

Abstract Background As an alternative to advection, solute transport by shear-augmented dispersion within oscillatory cerebrospinal fluid flow was investigated in small channels representing the basement membranes located between cerebral arterial smooth muscle cells, the paraarterial space surrounding the vessel wall and in large channels modeling the spinal subarachnoid space (SSS). Methods Geometries were modeled as two-dimensional. Fully developed flows in the channels were modeled by the Darcy–Brinkman momentum equation and dispersion by the passive transport equation. Scaling of the enhancement of axial dispersion relative to molecular diffusion was developed for regimes of flow including quasi-steady, porous and unsteady, and for regimes of dispersion including diffusive and unsteady. Results Maximum enhancement occurs when the characteristic time for lateral dispersion is matched to the cycle period. The Darcy–Brinkman model represents the porous media as a continuous flow resistance, and also imposes no-slip boundary conditions at the walls of the channel. Consequently, predicted dispersion is always reduced relative to that of a channel without porous media, except when the flow and dispersion are both unsteady. Discussion/conclusions In the basement membranes, flow and dispersion are both quasi-steady and enhancement of dispersion is small even if lateral dispersion is reduced by the porous media to achieve maximum enhancement. In the paraarterial space, maximum enhancement R max = 73,200 has the potential to be significant. In the SSS, the dispersion is unsteady and the flow is in the transition zone between porous and unsteady. Enhancement is 5.8 times that of molecular diffusion, and grows to a maximum of 1.6E+6 when lateral dispersion is increased. The maximum enhancement produces rostral transport time in agreement with experiments.

Diagnostic testing to detect forest pathogens requires the collection of physical samples from affected trees, which can be challenging in remote or rugged environments. As an alternative to traditional ground-based sampling at breast height by field crews, we examined the feasibility of aerially sampling and testing material collected from upper canopy branches using a small unoccupied aerial system (sUAS). The pathogen of interest in this study is Ceratocystis lukuohia, the fungal pathogen responsible for Ceratocystis wilt of ‘ōhi‘a, a vascular wilt disease which has caused widespread mortality to ‘ōhi‘a in native forests across the state of Hawai‘i. To characterize the minimum branch diameter needed to successfully detect the pathogen of interest in infected trees, we tested 63 branch samples (0.8–9.6 cm in diameter) collected from felled trees inoculated with C.lukuohia on Hawai‘i Island. Subsequently, we aerially sampled branches from ten symptomatic ‘ōhi‘a (Metrosideros polymorpha) trees using two different branch sampling systems, the Flying Tree Top Sampler from ETH Zurich and the new Kūkūau branch sampler system introduced in this work, producing 29 branch samples with a maximum diameter of 4.2 cm and length of >2 m. We successfully detected the target fungal pathogen from the collected branches and found that branch diameter, leaf presence and condition, as well as wood moisture content are important factors in pathogen detection in sampled branches. None of the smallest branch samples (those C.lukuohia, while 77% of the largest diameter branch samples (5–10 cm) produced positive results. The Kūkūau branch sampler system is capable of retrieving branches up to 7 cm diameter, providing important capacity for pathogenic research requiring larger diameter samples for successful diagnostic testing. Inconclusive and/or non-detection laboratory results were obtained from sample materials that were either too desiccated or from a branch with asymptomatic leaves, suggesting there is an optimal temporal window for sampling.

The United Nations Convention on Biological Diversity was established in 1993. Canada is a signatory nation that has adopted, and exceeded, the UN Aichi biodiversity target to protect 10% of coastal and marine areas through marine protected areas or “other effective area-based conservation measures” (OECMs) by 2020. However, the science of OECMs as contributors to biodiversity conservation is relatively young and their definition and efficacy testing continue to evolve. Here, we examine whether areas closed to fishing on the Scotian Shelf in Atlantic Canada, where the groundfish community had collapsed in the early 1990s, have the potential to serve as OECMs for groundfish recovery. Using long-term research survey data, we show that three long-term area-based fishing fleet closures did not enhance per capita population growth rates of the majority of 24 common groundfish species. At a regional scale, 10 out of 24 species are currently at less than 50% of their pre-collapse (1979–1992) biomass, reflecting a sustained diminished productivity, even though fishing mortality has been drastically reduced through a moratorium in 1993. Additional measures are needed to protect severely depleted groundfish, especially when the causes of continued diminished productivity are still largely unresolved. The importance of OECMs as a risk-averse approach toward sustainability is globally accepted and they can be considered a tool toward the overarching UN Sustainable Development Goals (SDG-14). Our study provides further impetus toward articulating the criteria of OECMs and improving their design, monitoring, and testing, while placing OECMs within the broader context of sustainable ecosystem-based management.

The American Cancer Society has estimated an expected 279,100 new breast cancer cases, and an expected 42,690 breast cancer deaths in the U.S. for the year 2020. This includes an estimated 276,480 women who are expected to be diagnosed. Radiation therapy, also called ionizing radiation therapy, is one of the most frequently used methods in the treatment of breast cancer. While radiation therapy is used in the treatment of more than 50% of all cancer cases, tumor resistance to ionizing radiation presents a major challenge for effective cancer treatment. Most tumor cells are in a hypoxic microenvironment that promotes resistance to radiation therapy. In addition to radiation resistance, the hypoxic microenvironment also promotes cancer proliferation and metastasis. In this review, we will discuss the hypoxic microenvironment of breast cancer tumors, related signaling pathways, breast cancer stem-like cells, and the resistance to radiation therapy. Recent developments in our understanding of tumor hypoxia and hypoxic pathways may assist us in developing new strategies to increase cancer control in radiation therapy.

Modern data and computational resources, coupled with algorithmic and theoretical advances to exploit these, allow disease dynamic models to be parameterised with increasing detail and accuracy. While this enhances models’ usefulness in prediction and policy, major challenges remain. In particular, lack of identifiability of a model’s parameters may limit the usefulness of the model. While lack of parameter identifiability may be resolved through incorporation into an inference procedure of prior knowledge, formulating such knowledge is often difficult. Furthermore, there are practical challenges associated with acquiring data of sufficient quantity and quality. Here, we discuss recent progress on these issues.

How do Mexicans of distinct racial backgrounds fit into the recognized patterns of racial health disparities? We conduct regression analyses using data from the 2000-2017 National Health Interview Survey to determine if Mexicans who self-identify as White or Black have a relative advantage or disadvantage in self-rated health in relation to Non-Hispanic (NH) Whites and Blacks in the U.S. Our results indicate that both Black Mexicans and White Mexicans have a significant disadvantage in relation to NH-Whites while White Mexicans have a slight advantage in relation to both NH-Blacks and Black Mexicans. Overall, our results suggest that studying health outcomes among Hispanics without considering race may mask inequalities not observed in the aggregate.

The behaviour of many processes in science and engineering can be accurately described by dynamical system models consisting of a set of ordinary differential equations (ODEs). Often these models have several unknown parameters that are difficult to estimate from experimental data, in which case Bayesian inference can be a useful tool. In principle, exact Bayesian inference using Markov chain Monte Carlo (MCMC) techniques is possible; however, in practice, such methods may suffer from slow convergence and poor mixing. To address this problem, several approaches based on approximate Bayesian computation (ABC) have been introduced, including Markov chain Monte Carlo ABC (MCMC ABC) and sequential Monte Carlo ABC (SMC ABC). While the system of ODEs describes the underlying process that generates the data, the observed measurements invariably include errors. In this paper, we argue that several popular ABC approaches fail to adequately model these errors because the acceptance probability depends on the choice of the discrepancy function and the tolerance without any consideration of the error term. We observe that the so-called posterior distributions derived from such methods do not accurately reflect the epistemic uncertainties in parameter values. Moreover, we demonstrate that these methods provide minimal computational advantages over exact Bayesian methods when applied to two ODE epidemiological models with simulated data and one with real data concerning malaria transmission in Afghanistan.

Globally, economies and marine ecosystems are increasingly dependent on sustainable fisheries management (SFM) to balance social, economic, and conservation needs. The overarching objectives of SFM are to maximize both conservation and socio-economic benefits, while minimizing short-term socio-economic costs. A number of tools have been developed to achieve SFM objectives, ranging from fishery specific to ecosystem-based strategies. Closures are a common SFM tool used to balance the trade-off between socio-economic and conservation considerations; they vary in scope from small-scale temporary closures to large-scale permanent networks. Unfortunately, closures are frequently implemented without a plan for monitoring or assessing whether SFM objectives are met. In situations in which a monitoring plan is not in place we propose that commonly available fishery data can often be used to evaluate whether management tools are effective in meeting SFM objectives. Here, we present a case study of closures on Georges Bank that shows how fishery data can be analyzed to perform such an assessment. Since 2006, on the Canadian side of Georges Bank, seasonal scallop fishery closures have been implemented with the aim of reducing by-catch of Atlantic cod (Gadus morhua) and yellowtail flounder (Pleuronectes ferruginea) during spawning. In lieu of data from a dedicated monitoring program, we analyzed data from Vessel Monitoring Systems (VMS), fishery logbooks, and a scallop survey to assess the impact of these closures on the scallop fishery, and use observer data (i.e. by-catch) to assess the effectiveness of these closures in meeting their conservation objective. While compliance for these time-area closures was high, the closures did not significantly displace fishing activity and overall there was limited evidence of an impact on the scallop fishery. Further, the discard rates for both cod and yellowtail were above average when their respective closures were active. These results suggest that improvements to the closures design and/or other measures may be required to achieve the desired SFM objectives.

Hawaii has long been one of the last coffee-producing regions of the world free of coffee leaf rust (CLR) disease, which is caused by the biotrophic fungus Hemileia vastatrix. However, CLR was detected in coffee farms and feral coffee on the island of Maui in February 2020 and subsequently on other islands of the Hawaiian archipelago. The source of the outbreak in Hawaii is not known, and CLR could have entered Hawaii from more than 50 coffee-producing nations that harbor the pathogen. To determine the source(s) of the Hawaii inoculum, we analyzed a set of eleven simple sequence repeat markers (SSRs) generated from Hawaii isolates within a dataset of 434 CLR isolates collected from 17 countries spanning both old and new world populations, and then conducted a minimum spanning network (MSN) analysis to trace the most likely pathway that H. vastatrix could have taken to Hawaii. Forty-two multilocus genotypes (MLGs) of H. vastatrix were found in the global dataset, with all isolates from Hawaii assignable to MLG 10 or derived from it. MLG 10 is widespread in Central America and Jamaica, making this region the most probable source of inoculum for the outbreak in Hawaii. An examination of global weather patterns during the months preceding the introduction of CLR makes it unlikely that the pathogen was windborne to the islands. Likely scenarios for the introduction of CLR to Hawaii are the accidental introduction of spores or infected plant material by travelers or seasonal workers, or improperly fumigated coffee shipments originating from Central America or the Caribbean islands.

Tayeb Salih’s Season of Migration to the North (1967) is understandably one of the best-known Arabic novels, and its English translation is probably the most widely read Arabic novel in English. This paper demonstrates that Season of Migration to the North is in many ways a classic postcolonial novel, concerned both with the British colonization of Sudan and with the postcolonial legacy of British rule. It also engages in direct dialog with British literature. For example, it has been frequently seen as a sort of rejoinder to Joseph Conrad’s Heart of Darkness. But Season of Migration to the North is a sophisticated literary work that has much in common with works of European modernism, even as it writes back to them. In fact, Salih’s novel has a particularly large number of points of contact with the work of James Joyce – perhaps the greatest of all European modernists but also a postcolonial writer in his own right.

Drought conditions can alter the composition of soil microbial communities, but the effects of drought on network properties have not been tested. Here, de Vries and colleagues show that co-occurrence networks are destabilised under drought for bacteria but not fungi.

Karst forests are often located in mountainous regions, and because of various geological factors both soil and water loss are major conservation concerns. We investigated the water-holding characteristics of 3 typical karst forest types through field sampling and laboratory experiments. The results showed that (1) the total litter mass of the coniferous forest was significantly higher than that of either the mixed forest or the broadleaved forest; (2) the mass of semidecomposed litter was significantly higher than that of undecomposed litter; (3) the litter layers of the mixed and coniferous forests had similar maximum water-holding capacity, whereas the maximum water-holding capacity of the broadleaved forest was significantly lower; (4) the maximum water-retention capacity of both the mixed and coniferous forests was significantly higher than that of the broadleaved forest; and (5) water-absorption rate and maximum water-holding capacity varied significantly across forest and litter types, with the mixed forest and undecomposed litter layers tending both to hold more water and to absorb water more quickly than the other forest types or the semidecomposed litter layer. Because of the elevated water-holding capacity and absorption rate of the mixed forest in karst regions, special emphasis on the conservation of this complex forest ecosystem is critical from both hydrological and ecological perspectives.